Expression of CD86 on human islet endothelial cells facilitates T cell adhesion and migration.
Pancreatic islet endothelial cells (ECs) form the barrier across which autoreactive T cells transmigrate during the development of islet inflammation in type 1 diabetes. Little is known about the immune phenotype of islet ECs that might shape their molecular interaction with autoreactive T cells before and during the development of islet inflammation. In this study we examined the expression and functional significance of costimulatory molecules by human islet ECs. Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules. The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone. Marked T cell proliferation in the coculture was completely abrogated by mAb blockade of CD86, confirming that costimulatory properties are conferred on ECs by CD86 expression. In view of its location on the vasculature, we hypothesized a role for CD86 in T cell adhesion/transmigration. In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb. Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects. These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
Lozanoska-Ochser
Biliana
B
King's College London, Department of Immunobiology, London, United Kingdom.
Klein
Nigel J
NJ
Huang
Guo C
GC
Alvarez
Raymond A
RA
Peakman
Mark
M
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D060908:CTLA-4 Antigen; D002448:Cell Adhesion / Q000276:immunology; D002464:Cell Migration Inhibition / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D060945:Inducible T-Cell Co-Stimulator Ligand; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008833:Microcirculation / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D008024:Ligands